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PubMedDate not supplied

Effects of lead exposure on GnRH and LH secretion in male rats: response to castration and alpha-methyl-p-tyrosine (AMPT) challenge.

Animal and clinical studies suggest that lead exposure disrupts the hypothalamic-pituitary axis. To define more precisely the toxic action of lead on the hypothalamic-pituitary unit, a series of in vivo and in vitro experiments were performed. The first experiment was designed to determine whether lead exposure exerts an inhibitory effect on GnRH secretion as reflected by an enhanced inhibition of luteinizing hormone (LH) secretion in response to the tyrosine hydroxylase inhibitor methyl-p-tyrosine (AMPT). In the control animals, the AMPT dose had no significant effect on LH secretion, whereas LH fell significantly in the lead-treated animals. In experiments designed to evaluate the effects of lead exposure on the pattern of pulsatile release of gonadotropins castrated control and lead-dosed animals were cannulated, and serial blood sampling was performed. Baseline LH and follicle-stimulating hormone values were not statistically different between the control and lead-treated group. There were no significant differences noted in pulsatile patterns when the data were analyzed as groups. Pituitary cells harvested from lead-treated animals released significantly more LH that did the control animals. These data are consistent with the hypothesis that the signals between the hypothalamus and pituitary gland are disrupted by lead exposure in the intact animal. However, the lead-exposed castrated rat's hypothalamic-pituitary unit is able to adapt to the toxic effects of lead.

Adaptation, Physiological↗
PubMed1994

Castration and testosterone induced changes in the pinealocytes of roseringed parakeet, Psittacula krameri, during different phases of the annual testicular cycle.

The pinealocytes in male roseringed parakeets (Psittacula krameri) were studied following bilateral castration and/or therapeutic administration of testosterone during the preparatory (June-July), progressive (Nov.-Dec.), pre-breeding (Jan.-Feb.) and breeding (March-April) phases of the annual testicular cycle. The responses of the pineal to either treatment were found to be almost identical throughout the investigation. In each reproductive phase, the pineal appeared to be hypertrophied following castration and the effect was reversed by therapeutic administration of testosterone, while hormonal treatment to the intact parakeets induced regressive changes in the pinealocytes. Collectively, the results of the current study support the hypothesis that the testis through its hormone testosterone exerts inhibitory influences on the activity of pineal, and may thus be considered as being involved in the determination of an inverse relationship between the pineal and the testis during the annual cycle of free-living parakeets.

Animals↗
PubMed1992

Analogues of LHRH versus orchidectomy: comparison of economic costs for castration in advanced prostate cancer.

Analogues of luteinising hormone releasing hormone (LHRH) have recently been introduced as an alternative to surgical orchidectomy in prostate cancer, but there has been concern about the economic costs of long-term treatment. The paper presents a comparison of costs for LHRH analogues versus orchidectomy in patients with advanced prostate cancer. The cost for the surgical procedure was estimated using data on patients treated with orchidectomy in Stockholm County, Sweden, during 1981-86. Estimates of costs for treatment with a depot LHRH analogue was based on observed treatment times among patients with symptomatic prostate cancer in a British randomised clinical trial of medical castration versus surgical orchidectomy. The average cost for orchidectomy was estimated at 2,580 pounds i.e. 7-31% less than for treatment with a depot LHRH analogue (2,760 pounds-3,380 pounds) assuming a mean treatment time in the range 19-23 months. The most cost-effective policy for castration was found to be initial treatment with an LHRH analogue followed by deferred orchidectomy after about 2 years among long-term responders. This policy would obviate the need for surgery in about 85% of the patients and the average cost (1,900 pounds) would be about 26% lower compared to that of a policy of primary orchidectomy in all patients.

Antineoplastic Agents↗
PubMed2003

The clinical implications of the difference between castration, gonadotrophin releasing-hormone (GnRH) antagonists and agonist treatment on the morphology and expression of GnRH receptors in the rat ventral prostate.

OBJECTIVE: To examine the effects of castration and continuous gonadotrophin releasing-hormone (GnRH) agonist and antagonist therapy on the expression of GnRH-receptors type I (GnRH-RI) in rat ventral prostate (VP) and pituitary tissue, and to compare the effects on prostate morphology. MATERIAL AND METHODS: Mature Sprague-Dawley rats were assigned to four treatment groups: group 1, vehicle only; group 2, GnRH agonist goserelin (100 microg/rat/day); group 3, GnRH antagonist cetrorelix (100 microg/rat/day); and group 4, orchidectomy. After 4 weeks the body weights were recorded and VP and pituitary tissue analysed for GnRH-RI expression using a competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: GnRH antagonist and orchidectomy decreased testosterone secretion and VP volume similarly, but the effects were not identical. The involution of the glandular lumina was more pronounced after orchidectomy while the antagonist therapy was more effective in suppressing epithelial cell proliferation. In the VP, GnRH-RI mRNA levels were increased after GnRH analogue therapy, but were unaffected by orchidectomy. In the pituitary, GnRH-RI mRNA expression was higher in response to orchidectomy and decreased after GnRH analogue treatment. CONCLUSION: Treatment with a GnRH antagonist for 4 weeks is more effective than an agonist in suppressing testosterone and inducing VP involution. The GnRH antagonist was more effective in suppressing VP epithelial cell proliferation than was castration, suggesting that it induces reduced proliferation by interfering with effects of locally produced GnRH. These results suggest that different regulatory mechanisms may operate in the rat VP than in the pituitary to control GnRH-RI mRNA expression.

Animals↗
PubMed2000

Effects of acute pain reduction methods on the chronic inflammatory lesions and behaviour of lambs castrated and tail docked with rubber rings at less than two days of age.

Lesions were produced by castration and tail docking of two-day-old Dorset-cross lambs with elastrator rings with (RRla) and without (RR) local anaesthetic or after destruction of the innervation by crushing close to the ring (Brr). The lesions were monitored twice weekly for six weeks and the behaviour of handled controls (H), RR and RRla lambs was recorded for two 3 h periods 10, 20, 31 and 41 days after treatment. There was no significant effect of castration and tail docking, with or without pain reduction methods, on daily liveweight gain. In the Brr lambs, the dead tails were cast 10 days earlier than from RR and RRla lambs. The time taken for the scrotal lesion to reach maximum severity was halved in Brr and RRla lambs, although the maximum severity of the lesion was unaffected by the methods of pain reduction. During the four 6 h behavioural observation periods, RR lambs showed a significant increase in the mean (+/- sd) frequency of foot stamping (RR13 +/- 13; H2 +/- 2.5), tail wagging (61 +/- 26; 15 +/- 6), head turning to the scrotum and inside hind-leg (12 +/- 10; 1 +/- 1). Less abnormal behaviour was found after RRla than after RR treatment. This unexpected finding may be evidence of long-lasting increases in pain sensitivity after an episode of intense acute pain in young animals.

Animal Welfare↗
PubMed2000

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer.

D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 microg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 microg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders.

Aged↗
PubMed1988

Steroid and steroid regulating hormones in human male castrates.

Testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone and its sulphate, 11 beta-hydroxyandrostenedione, 17 alpha-hydroxyprogesterone, cortisol, LH, FSH and sex hormone binding globulin (SHBG) were determined in 16 otherwise healthy male castrates, orchidectomized for the forensic reasons. Their hormone levels were compared with those, obtained in normal males of the same age category. There were found in the castrates decreased levels of testosterone, dihydrotestosterone, dehydroepiandrosterone sulphate and androstenedione, unaltered concentrations of cortisol and dehydroepiandrosterone, whereas the levels of 11 beta-hydroxyandrostenedione, 17 alpha-hydroxyprogesterone, both gonadotrophins and SHBG were increased. The results point to the importance of the selective increase of the incretory activity of the adrenal cortex in situations, when the gonadal function is impaired or missing.

Adrenal Cortex↗
PubMed1990

Testosterone increases TSH-beta mRNA, and modulates alpha-subunit mRNA differentially in mouse thyrotropic tumor and castrate rat pituitary.

TSH, LH and FSH, the three pituitary glycoprotein hormones, are each composed of a common alpha-subunit and a hormone specific beta-subunit. Testosterone is known to regulate all three intact hormones differently in the rodent. However, there is only one gene encoding the common alpha-subunit. In order to elucidate the effects of testosterone on TSH subunit synthesis and its regulation of the common alpha-subunit, two in vivo models were studied: castrate rat pituitary was used as a gonadotropin-enriched tissue; and mouse thyrotropic tumor was used as a thyrotropin-enriched tissue. Male castrate rats were treated with testosterone propionate, 500 micrograms/100 g BW, sc, for 11 days. Testosterone increased plasma TSH to 131% of control values (P less than 0.02), while plasma LH fell to undetectable levels, and plasma alpha-subunit fell to 14% of control values (P less than 0.001). Testosterone increased TSH-beta mRNA to 237% of control values (P less than 0.02), while alpha-subunit mRNA fell to 20% of control values (P less than 0.001). Hypothyroid mice bearing thyrotropic tumors were treated with testosterone propionate, 150 micrograms/100 g BW, sc, for 11 days. In this model plasma TSH-beta and alpha-subunit concentrations are 1000-fold higher than in non-tumor bearing animals, and the contribution of pituitary gonadotropes to plasma subunit concentrations is negligible. "Total" TSH-beta and alpha-subunit concentrations were estimated as one-half of intact TSH plus the respective free subunit concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Castration reversibly alters levels of cholecystokinin immunoreactivity within cells of three interconnected sexually dimorphic forebrain nuclei in the rat.

Three sexually dimorphic cell groups in the forebrain of the rat--the central part of the medial preoptic nucleus, the encapsulated part of the bed nucleus of the stria terminalis, and the posterodorsal part of the medial nucleus of the amygdala--are larger in males, contain a high density of gonadal-steroid-concentrating cells, and are thought to play important roles in the control of reproductive behavior and physiology. Since each of these regions contains a large number of cholecystokinin-immunoreactive cells, we used an indirect immunohistochemical method to examine the possibility that levels of this peptide are modulated by circulating gonadal steroids in adult male rats. Rats were castrated at 60 days of age, and one group each was pretreated with colchicine and then killed 3, 7, and 14 days after gonadectomy. Castration clearly decreased CCK immunoreactivity within cells of each region, with the most dramatic effects occurring 7 and 14 days after gonadectomy, and these effects were reversed by treatment with testosterone over a 14-day period. The results suggest that CCK levels within individual cells in each of the interconnected sexually dimorphic nuclei examined here are regulated by circulating gonadal steroids and may be related to the hormonal modulation of reproductive functions thought to be mediated by these cell groups.

Animals↗
PubMed2006

Individual variation of hormonal recovery after cessation of luteinizing hormone-releasing hormone agonist therapy in men receiving long-term medical castration therapy for prostate cancer.

OBJECTIVE: To evaluate the process of hormonal recovery after cessation of luteinizing hormone-releasing hormone (LHRH) agonist treatment in patients who had received long-term LHRH agonist therapy for prostate cancer. MATERIAL AND METHODS: Men who had successfully undergone androgen deprivation therapy with only monthly LHRH agonist therapy for > 30 months were enrolled and the administration of LHRH agonist was discontinued. Serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prostate-specific antigen (PSA) were measured before the cessation of LHRH agonist therapy and every 4 weeks thereafter, and the administration of LHRH agonist remained suspended until the total testosterone level recovered to > 50 ng/dl. RESULTS: Ten patients were enrolled in the study. The median (range) castration period and the levels of serum LH, FSH, total testosterone and PSA at cessation of therapy were 39 (30-56) months,<0.5 (<0.5-1.8) mIU/ml, 6.4 (3.0-15.9) mIU/ml, 15.3 (5.8-34.7) ng/dl and 0.13 (0.02-0.89) ng/ml, respectively. Testosterone recovered to > 50 ng/dl in all cases. There were large variations in the times required for recovery of LH and FSH (30-100 days) and serum testosterone (30-330 days). PSA began to increase at various testosterone levels, and there was a large variation (0-83%; median 41%) in the ratio of the androgen suppression (testosterone < 50 ng/dl) time to the period of LHRH agonist cessation. CONCLUSIONS: There was considerable variation in the hypothalamus-pituitary-testicular hormone profiles during recovery from long-term medical castration. These findings are noteworthy when interruption of androgen deprivation therapy is applied with the intention of delaying the progression of hormone-refractory cancer or improving the patient's quality of life.

Aged↗
PubMed1991

Effects of repeated handling on the cortisol responses of young lambs castrated and tailed surgically.

Changes in the plasma concentrations of cortisol were recorded in 5-6 weeks-old lambs during the first 480 minutes after surgical castration and tailing in order to define the full post-treatment cortisol response and to determine whether or not the handling associated with repeated blood sampling delayed the return of cortisol concentrations to pretreatment values. Four groups of six or seven lambs were studied: One group was bled regularly throughout the 480 minutes of the study, and in the other three post-treatment blood sampling began at 90, 240 or 480 minutes. Plasma cortisol concentrations increased after treatment and returned to or approached pretreatment values by 480 minutes. No significant differences in mean cortisol concentrations were observed between the groups at any stage. It is concluded that the acute distress response of these lambs to surgical castration and tailing lasted about 8 hours and that repeated handling for blood sampling did not contribute significantly to this distress.

Journal Article↗
PubMed2005

Intraruminal infusion of n-butyric acid induces an increase of ruminal papillae size independent of IGF-1 system in castrated bulls.

The objective of this study was to explore morphological alterations of rumen papillae induced by n-butyric acid in relation to the insulin-like growth factor (IGF) system in adult castrated bulls. Three animals fitted with rumen cannula were fed twice daily at a low and high nutritional level (LL and HL), i.e., at 1.1 x maintenance (M) and 1.6 x M, respectively. Diets contained artificial dried grass and concentrate (74:26 and 52:48). Bulls received no (B0) or daily intraruminal infusions of 500 g n-butyric acid (B500) over 14 d. The infusion started 1 h after the morning feeding (9:00) and lasted for 3.5 h. Thus, four treatments (BOLL, B500LL, BOHL, and B500HL) were compared. Blood and rumen mucosa samples from the atrium ruminis were taken at the last day of each period. Length, width and surface of rumen papillae were greater (p < 0.001) in BOHL than in BOLL. Treatment with n-butyric acid resulted in an increase of the papillae surface of 20-40% (p = 0.047) for both nutritional levels as compared to periods without n-butyric acid treatments. The higher nutritional level and intraruminal n-butyric acid infusion induced epithelial cell death. The percentage of proliferative cells was doubled by n-butyric acid treatment. The mRNA of IGF-1 and IGF type 1 receptor (IGF-1R), as well as IGF-1R binding capacity were unaffected by butyric acid treatments. The abundance of IGF-1 mRNA tended to be lower (p = 0.1) and IGF-1R abundance was lower (p = 0.03) in response to the HL. The plasma IGF-1 concentration was lower with butyric acid treatment (p < 0.01), but was unaffected by the nutritional level. In conclusion, under described experimental preconditions of daily short-time intraruminal n-butyric acid infusion alterations of rumen papillae morphology is not mediated by ruminal IGF type 1 receptor and by local IGF-1 expression in papillae in castrated bulls.

Animal Nutritional Physiological Phenomena↗
PubMed1987

The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin.

The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.

Aflatoxins↗
PubMed1989

The influence of unilateral castration on testicular morphology and function in adult rams.

An experiment was designed to investigate the mechanisms controlling testicular compensatory hypertrophy in rams. Endocrine and histological events were examined, with special attention to Sertoli cell hyperplasia and hypertrophy as contributing factors to the compensatory process. Fifteen sexually mature yearling Targhee rams were allotted to intact control (C, n = 5) and unilateral castrate (UC, n = 10) treatment groups in June. Approximately 150 days after UC, testicular tissue was collected in November after efferent duct cannulation and rete testis fluid (RTF) collection or perfusion fixation. Unilateral castration increased mean testis weight by 56% (p = 0.01) and mean epididymal weight by 15% (p = 0.05). Although the mean volume of RTF collected more than doubled after UC (1.55 +/- 0.86 vs. 0.63 +/- 0.10 ml for UC and C rams, respectively), the difference was not statistically significant. By 150 days after UC, the concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) in jugular venous blood did not differ between the two treatment groups. The concentrations of T. dihydrotestosterone (DHT), and androgen-binding protein (ABP) in RTF were also similar for UC and C rams. However, since the observed mean RTF volume was increased, the amounts of T, DHT, and ABP exiting the testes of these UC rams via the RTF were approximately doubled, although this difference was not statistically significant. UC increased the mean diameter of seminiferous tubules by 21% (p less than 0.01) and of their lumina by 51% (p less than 0.01), but did not significantly increase mean height of seminiferous epithelium or estimated length of seminiferous tubules per testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Equivalent levels of mating-induced neural c-fos immunoreactivity in castrated male rats given androgen, estrogen, or no steroid replacement.

The nuclear protein product (FOS) of the immediate-early gene, c-fos, was visualized immunocytochemically in the brains of male rats after they either achieved 8 intromissions with an estrous female or were left alone in a test arena. Mating induced equivalent increments in the number of FOS immunoreactive (IR) neurons present in the medial preoptic area (mPOA), the bed nucleus of the stria terminalis (BNST), and the medial amygdala in groups of males that were gonadally intact or had been castrated and treated for 7 days with either testosterone propionate, dihydrotestosterone propionate, estradiol benzoate (EB), or oil vehicle. Equivalent, low numbers of FOS-IR neurons were seen in these brain regions in additional groups of castrated males that received either EB or oil vehicle but were not paired with a female before being killed. Circulating sex steroids apparently contribute little to the mating-induced stimulation of c-fos gene expression, even in brain regions known to contain high levels of androgen and estrogen receptor.

Amygdala↗
PubMed1996

Differential pituitary and gonadal function of Chinese Meishan and European white composite boars: effects of gonadotropin-releasing hormone stimulation, castration, and steroidal feedback.

Considerable breed differences exist in concentrations of gonadotropins between Chinese Meishan boars and meat-type crossbred boars of European origin. To define mechanisms that might be responsible, sensitivity to GnRH stimulation, hormonal clearance, and gonadal pituitary feedback effects were monitored in two experiments. In the first trial, jugular catheters were placed into mature Meishan (n = 7) and white composite boars (n = 8). Boars were repetitively sampled after administration of two doses of GnRH (150 and 1500 ng/kg BW) a week apart. Before administration of GnRH, FSH was greater in Meishan boars (554 +/- 50 vs. 102 +/- 8 ng/ml, p < 0.01). Both breeds responded with increases in FSH, LH, and testosterone; but concentrations of gonadotropins in Meishan boars were increased for a greater duration than in white composite boars. By 160 min after GnRH administration, gonadotropins were declining in white composite boars. Maximal plasma concentrations of FSH after GnRH stimulation were greater with the higher GnRH dosage than with the lower (1058 +/- 113 vs. 730 +/- 70 in Meishan and 184 +/- 40 vs. 141 +/- 14 ng/ml in white composite boars). In the second trial, boars were assigned to three groups related to their circulating FSH concentrations: European white composite boars (FSH = 100 ng/ml), Meishan boars with low FSH (FSH = < 500 ng/ml), and Meishan boars with high FSH (FSH > 750 ng/ml; n = 5 per breed group). Boars were cannulated and repetitively sampled during three protocols: 1) low GnRH stimulation (15 ng/kg BW), 2) pre- and postcastration, and 3) steroidal treatment (0.5 mg testosterone propionate and 20 micrograms estradiol cypionate/kg BW; then 24 days later, a 20-strength low-dosage steroid treatment). At the low GnRH stimulation, LH and testosterone concentrations were increased but FSH concentrations were not altered. Rate of increase of FSH and decline of testosterone concentrations were not different between the three treatment groups after castration. Castration levels of FSH were maintained and further increased with time. Rates of reduction in FSH concentration after gonadal steroidal stimulation were not different between breed groups, but Meishan boars escaped the exogenous steroid suppression earlier than white composite boars (p < 0.01). Differences in concentrations of gonadotropins in Meishan and white composite boars of European origin seem to be at the pituitary level of control and not related to gonadal factors.

Animals↗
PubMed1989

Influence of steroids on the exocrine pancreas: presence of laminated bodies in the acinar lumen following castration and adrenalectomy.

The influences of combined adrenalectomy and castration and of a replacement therapy with estradiol and glucocorticoids were examined in the rat pancreas. At the light microscope level, the surgical treatment changed the overall shape of the acini and caused widening of intralobular and interlobular spaces as well as partial depletion of zymogen granules. A significant reduction of the acinar lumen size was observed in castrated-adrenalectomized (CasX-AdreX) animals. This could be reversed by a replacement therapy with glucocorticoids. Moreover, triamcinolone even caused a significant lumen enlargement as compared to sham-operated animals. Such an enlargement was not observed with dexamethasone. Both these glucocorticoids caused an increase in zymogen granule content of the acinar cell. At the ultrastructural level, hitherto undescribed type of precipitates was observed in the acinar lumen of CasX-AdreX rats. Precipitates that exhibited a laminated aspect were identified as luminal laminated bodies. The latter could have some interest from the etiological point of view of certain pancreatic diseases, such as cystic fibrosis and pancreatitis. Replacement therapy with estradiol did not affect the frequency of these precipitates, but glucocorticoid had a significantly inhibitory effect. From our observation, it is clear that some steroid exert a profound influence on the acinar cell and that a replacement therapy with glucocorticoids or estradiol do not totally restore the normal aspect of the pancreas acinar tissue. It suggests that some unknown factors from adrenals or testis are still required in addition to glucocorticoids and estrogens for the maintenance of the structural integrity of the gland.

Adrenalectomy↗
PubMed2005

Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene.

OBJECTIVE: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. DESIGN: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. RESULTS: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. CONCLUSIONS: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗